Abstract: Whole genome sequencing (WGS) allows exploration of the complete compendium of oncogenic processes generating characteristic patterns of mutations. Mutational signatures provide clues to tumour aetiology and highlight potentially targetable pathway defects. Here, alongside single base substitution (SBS), double base substitution (DBS), small insertions and deletions (ID) and copy number aberration (CN) signatures covered by the Catalogue of Somatic Mutations in Cancer (COSMIC) we report signatures from an additional mutation type, structural variations (SV), all extracted de-novo from WGS in 10,983 patients across 16 tumour types recruited to the 100,000 genomes project. Across the five mutation classes we report 137 signatures, with 29 signatures new to COSMIC, including the first COSMIC SV signature reference set. We relate the signatures to clinical outcomes and likely response to therapy, demonstrating the role of signature analysis in delivering the vision of precision oncology.